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PubMed2026

Effects of exercise on muscle strength and characteristics in rheumatic diseases and sarcopenia: Protocol for the Care for Muscle (C4M) Study.

OBJECTIVE: Muscle weakness is prevalent in rheumatoid arthritis (RA), osteoarthritis (OA) and sarcopenia (SARC). Endurance exercises may improve mitochondrial function and oxidative capacity, while strength exercises are thought to stimulate myofibrillar protein synthesis. This study aims to compare the effects of strength and endurance exercise and explore the association between muscle characteristics and exercise outcomes in patients with RA, OA and SARC. We hypothesize that responses to endurance and strength exercises in patients with muscle weakness are influenced by intramuscular pathology including muscle morphology, mitochondrial function, and systemic inflammation, based on their disease pathology, potentially requiring personalized training schedules. METHODS: This two-arm, parallel-group exploratory trial will enroll 69 patients (23 RA, 23 OA, 23 SARC), randomized to endurance (n = 35) or muscle strength exercises (n = 34), using minimization to balance disease type and gender. The 8-week intervention includes two supervised sessions per week using a controlled cable pulley device (Reforter™) and fitness equipment, plus one weekly home-based session. The primary outcome is isokinetic muscle strength (peak torque), measured with the Biodex system®. Secondary outcomes include muscle morphology, mitochondrial function, systemic inflammation and muscle endurance (by Biodex and 6 Minute Walk test). Muscle morphology will be assessed via 3D ultrasound imaging of the vastus lateralis. Mitochondrial function will be analyzed using high-resolution respirometry on muscle biopsies. Systemic inflammation will be measured using multiplex assays or ELISA on serum samples. DISCUSSION: This study will explore differential responses to muscle endurance and muscle strength exercises in patients with RA, OA, and SARC, offering novel insights into the molecular mechanisms of muscle weakness. The findings may help identify potential mechanisms underlying variability in exercise response and provide effect size estimates to guide future confirmatory studies and more targeted exercise interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT06480643 (date of registration28-06-24).

Humans↗

PubMed2026

ADAM10's combined influence on the diagnostic usefulness of IL 22, IL 10, IL-17 A, and IL-17D in autism spectrum disorders: Predicted role on gut leakiness as co-morbidity.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with increasing global prevalence but a lack of reliable diagnostic biomarkers. Emerging evidence suggests that immune dysregulation, gut-brain axis dysfunction, and increased intestinal permeability play key roles in ASD pathophysiology. This study investigated the combined diagnostic value of ADAM10 and cytokines (IL-10, IL-22, IL-17 A, and IL-17D). Multivariable logistic regression produces an improved ROC curve that improves diagnostic accuracy over individual markers by combining numerous predictors into a single risk score (linear predictor). The technique, which frequently raises individual marker AUCs, entails modelling a binary result, calculating the probability, and visualizing ROC based on the projected probabilities. In this case-control study, plasma levels of ADAM10, IL-10, IL-22, IL-17 A, and IL-17D were measured in 37 male children with ASD and 37 age-matched controls. Group comparisons, correlation analyses, and receiver operating characteristic (ROC) curve analyses, including combined ROC models, were performed. ADAM10, IL-22, and IL-17 A levels were significantly reduced in children with ASD compared to controls, whereas IL-10 and IL-17D showed no significant differences. ADAM10, IL-17 A, and IL-22 demonstrated good diagnostic performance, with AUC values of 0.886, 0.855, and 0.812, respectively. In contrast, IL-10 and IL-17D showed poor discriminatory ability, with AUC values of 0.524 and 0.599, respectively. Combined ROC analysis markedly improved diagnostic accuracy, with all panels including ADAM10 achieving AUC values above 0.90, and some reaching as high as 0.988, with high sensitivity and specificity. The combination of ADAM10 with selected cytokines significantly enhances diagnostic performance compared to individual markers, supporting a link between immune dysregulation, barrier dysfunction, and gut permeability in ASD.

Humans↗

PubMed2026

Unveiling the power of TIIC: A prognostic tool for esophageal adenocarcinoma.

BACKGROUND: Esophageal adenocarcinoma (EAC) remains a lethal malignancy with limited prognostic tools for guiding immunotherapy. Tumor-infiltrating immune cells (TIICs) play a critical role in EAC prognosis and treatment response. METHODS: We integrated single-cell RNA sequencing and bulk transcriptome data from TCGA and GEO databases. TIIC-specific RNAs were identified via tissue specificity index calculation combined with machine learning feature selection. Twenty machine learning algorithms were benchmarked to construct an optimal TIIC signature score (TIIC-Score) based on the comprehensive C-index. Immunotherapy response, genomic mutation, and copy number variation were analyzed. Summary-data-based Mendelian randomization (SMR) and two-sample Mendelian randomization (MR) were performed to explore genetic associations. Core prognostic TIIC-related genes were functionally validated in esophageal cancer cell lines through loss-of-function assays. RESULTS: The TIIC-Score demonstrated robust prognostic value for 1-, 2-, and 3-year overall survival across multiple cohorts, outperforming 22 published models. High TIIC-Score was associated with poor survival and increased chromosomal instability. Mutation profiling revealed high frequencies of TP53 (78.2%), TTN (48.7%), and SYNE1 (30.8%). MR analysis identified a significant association between gastro-oesophageal reflux and EAC risk at SNP rs8130507. Functionally, CCNI was upregulated in esophageal cancer cells, and its knockdown suppressed malignant phenotypes while promoting apoptosis, supporting its pro-tumorigenic role. CONCLUSION: The TIIC-Score provides a novel prognostic framework for EAC that effectively stratifies patient risk and may help identify individuals most likely to benefit from immunotherapy.

Esophageal adenocarcinoma↗

PubMed2026

Correlative analysis of endogenous miRNA expression profiles underlying brown planthopper adaptation to resistant rice.

The brown planthopper (Nilaparvata lugens Stål, BPH) is a major insect pest threatening global rice production. However, the molecular mechanisms underlying the adaptation of BPH populations with different virulence levels to resistant rice cultivars remain poorly understood. MicroRNAs (miRNAs), as key post-transcriptional regulators, play critical roles in host adaptation in herbivorous insects. In this study, we analyzed the miRNA expression profiles of a high-virulent population (IR56p) and a low-virulence population (TN1p) after feeding on susceptible (TN1) and resistant (IR56) rice cultivars. Our findings reveal distinct miRNA-mediated regulatory strategies employed by the two populations. The IR56p population showed downregulation of miRNAs including miR-10, miR-124, and miR-316, showing an inverse correlation with increased expression of predicted target genes involved in detoxification (carboxylesterase, UDP-glycosyltransferase) and effector function (calmodulin). In contrast, several miRNAs highly expressed in IR56p, including miR-307, miR-317, and miR-275, were predicted to target rice genes associated with hormone signaling, cell wall biosynthesis, and oxidative homeostasis, suggesting a possible but unproven inter-species regulatory role that requires functional validation. Collectively, these descriptive and correlative findings provide hypothesis generating insights into insect-plant coevolution and identifies candidate molecular targets for future functional validation and RNA interference-based pest management strategies.

Animals↗

PubMed2026

Systematic identification pepper CaE2F transcription factor reveals the role of CaDPb in drought stress response.

The EARLY 2 FACTOR (E2F) transcription factor (TF) family plays a pivotal role in regulating plant development and adaptations to environmental stresses. However, the physiological function of E2Fs in pepper (Capsicum annuum L.) are not well elucidated. In this work, we conduct a comprehensive genome-wide annotation of the E2F family within the Zunla-1 pepper genome and further explore the biological roles of CaDPb in response to drought stress. Through systematic bioinformatics analysis, we identify a total of nine CaE2F genes within the Zunla-1 genome, categorizing them into three distinct subgroups. Additionally, we discover multiple cis-regulatory elements in the CaE2F promoter regions associated with responses to plant hormones and drought stress. Public RNA-seq datasets reveal distinct expression profiles of CaE2F genes across various pepper tissues and their responses to environmental stimuli and plant hormones. Subsequently, the CaDPb gene is further functionally verified in drought response. Our findings indicate that TRV2:CaDPb silenced pepper plants are more sensitivity to drought. Furthermore, we show that CaDPb participates in the regulation of reactive oxygen species (ROS) production, the expression of drought-responsive genes, and the modulation of stomatal aperture. Taken together, our findings provide a comprehensive characterization of E2F genes in pepper and offer insights into the biological function of CaDPb in pepper drought stress response.

Capsicum↗

PubMed2026

The mighty microproteins: from versatile cellular regulators to precision medicine therapeutics.

Microproteins, are tiny proteins encoded by small open reading frame (sORF), translation of these non-canonical open reading frames (ncORFs) has been implicated in diverse biological processes and diseases. This review summarizes recent developments in the discovery, biogenesis, and functional characterization of microproteins, and their involvement in various disease, with special focus on their roles in cancer, cardiovascular, metabolic, neurodegenerative and immune-related disorders. We emphasize the regulation of key cellular pathways by microproteins, including mitochondrial homeostasis, apoptosis, metabolic reprogramming, and immune signaling, all of which affect disease initiation and progression. Emerging evidence also supports their potential as disease biomarkers and therapeutic candidates for precision medicine. Finally, the review critically discusses the current challenges including discrepancies in microprotein annotation, the limitations of ribosome profiling and proteogenomic approaches, the gap between computationally predicted and experimentally validated microproteins, and the need for rigorous orthogonal validation by means of CRISPR-based genome editing, ribosome release assays, mutational analysis, high-resolution mass spectrometry, and functional studies. Finally, we review recent development of AI-assisted ORF prediction, single-cell translatomics, spatial proteomics, and integrated multi-omics as emerging technologies reshaping. Microprotein discovery and functional annotation. Finally, we discuss the translational potential of microproteins and highlight the remaining challenges to clinical application, including peptide stability, pharmacokinetics, tissue-specific delivery, immunogenicity, and the need for rigorous preclinical and clinical validation. Together, this review provides an updated and critical overview of the rapidly evolving microprotein field and highlights future research priorities for translating these molecules into clinically useful biomarkers and precision therapeutics.

Microproteins↗

PubMed2026

Treatment-related associations of nucleus accumbens connectivity within mesocorticolimbic circuits in depression.

Pharmacological treatment remains a mainstay in managing depression, yet the neural correlates associated with treatment response remain incompletely understood. This study used multimodal neuroimaging to examine nucleus accumbens (NAc)-centered structural and functional alterations associated with fluoxetine and Shugan Jieyu Capsule (SG), a traditional Chinese medicine, in patients with mild-to-moderate depression (MMD). Sixty patients were randomized to an 8-week course of fluoxetine or SG. Depression severity was assessed using the 24-item Hamilton Depression Rating Scale (HAMD-24), and structural and functional MRI scans were acquired at baseline and endpoint. Both treatments were associated with significant symptom improvement. Neuroimaging analyses revealed structural and functional alterations involving the NAc. Changes in NAc-amygdala connectivity showed an exploratory association with symptom improvement in the SG group, whereas changes in NAc-rostral anterior cingulate cortex connectivity were associated with symptom improvement in the fluoxetine group and remained significant after correction for multiple comparisons. In addition, remitters exhibited stronger baseline connectivity between the NAc and ventral tegmental area and between the NAc and middle frontal gyrus compared with non-remitters. These findings suggest that NAc-centered connectivity may be relevant to treatment-related neural changes in depression and may inform future research on imaging-based candidate markers of treatment response and personalized treatment approaches. TRIAL REGISTRATION: The study is registered in https://www.chictr.org.cn/ with a registration number ChiCTR1900024988 (date: 08.06.2019).

Humans↗

PubMed2026

Comparative analyses of olfactory receptor repertoires in Schizothorax fish based on the chromosome-level genomes: Implications for regulatory roles of dietary differentiation and ploidy variation.

The olfactory receptor (OR) genes constitute the molecular basis of fish olfaction, mediating survival behaviors and environmental adaptation while coevolving with habitat-driven evolution. Schizothorax, a cyprinid genus endemic to the Qinghai-Tibetan Plateau, exhibits remarkable dietary divergence and ploidy variation in response to plateau environmental changes, which presumably facilitates the adaptive evolution of OR genes. However, the evolutionary patterns of OR genes associated with trophic divergence and ploidy variation in this genus remain unclear. In this study, three species were selected: the herbivorous diploid S. macropogon, the carnivorous diploid S. lantsangensis, and the herbivorous tetraploid S. curvilabiatus. S. macropogon possessed 142 OR genes (92.25% functional), primarily located on chromosomes 14 and 24, with the fewest sequence clusters. Such compact gene repertoire and highly overlapping chromosomal clusters indicated specialization for a herbivorous olfactory niche. S. lantsangensis contained 127 OR genes (93.70% functional), concentrated on chromosomes 4 and 5, with fewer sequence clusters and a scattered distribution, reflecting evolution of OR genes under carnivorous feeding habits. The herbivorous tetraploid S. curvilabiatus exhibited striking features: 316 OR genes (94.30% functional), the most subfamilies, unique ε and κ OR subfamilies, and species-specific motifs. These characteristics revealed that ploidy, rather than herbivory, dominated OR gene evolution. In conclusion, dietary differentiation and ploidy variation together drove olfactory adaptive evolution in Schizothorax, providing new insights into vertebrate OR gene ecological adaptation.

Animals↗

PubMed2026

Hydrogen-rich water combined with traditional Chinese medicine compound in the treatment of kidney stones: a randomized controlled prospective clinical trial.

JOURNAL/mgres/04.03/01612956-202701000-00009/figure1/v/2026-09-13T085902Z/r/image-tiff The formation and development of kidney stones are related to abnormal urine metabolism, oxidative stress and inflammation. Hydrogen-rich water has clear efficacy in antioxidant and improving inflammatory status, while Ye-Shi-Shi-Lin-Formula is a clinically effective traditional Chinese medicine compound preparation for treating kidney stones. This randomized controlled prospective clinical trial from July 2025 to March 2026 at the Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine examined the effect of hydrogen-rich water and Ye-Shi-Shi-Lin-Formula on kidney stones. The included 100 patients with kidney stones were randomly divided into blank, hydrogen-rich water, hydrogen-rich water and Chinese medicine, and Chinese medicines groups. The patients received drinking hydrogen-rich water and/or Ye-Shi-Shi-Lin-Formula daily for 12 weeks. All subjects received basic treatment following the guidelines. Imaging examination, urine metabolism testing, renal function, inflammation and oxidative stress index, blood routine and liver function are used to detect the efficacy and safety of hydrogen-rich water and Ye-Shi-Shi-Lin-Formula. Results showed that the total effective rate of kidney stone treatment in blank group, Chinese medicines group, hydrogen-rich water and Chinese medicine group and hydrogen-rich water group was 28%, 76%, 80% and 32%. The Ye-Shi-Shi-Lin-Formula can partially alleviate the oxidative stress, uric acid metabolism and urinary magnesium levels of patients with kidney stone and improve the function of renal tubules. The hydrogen-rich water therapy showed only efficacy in improving glutathione reductase but the combination of hydrogen-rich water and Ye-Shi-Shi-Lin-Formula has shown superior efficacy in improving oxidative stress and related metabolic factors of blood uric acid and urine stones, as well as in renal tubular function. The results indicate that the addition of hydrogen-rich water can improve urinary metabolism and oxidative stress status in the treatment of kidney stones with Ye-Shi-Shi-Lin-Formula. The study was registered at the International Traditional Medicine Clinical Trial Registry (Registration No. ITMCTR2025001446).

Humans↗

PubMed2026

Neurocorrelates of nocturnal enuresis in pre-adolescent children.

INTRODUCTION: Nocturnal enuresis (NE) is a common neurodevelopmental condition, yet its underlying neural mechanisms remain unclear. This study leverages the large-scale Adolescent Brain Cognitive Development (ABCD) dataset to identify structural and functional brain correlates associated with active symptoms and the resolution of bedwetting. METHODS: Using cross-sectional data from 3472 participants aged 9-10 years, children were categorized into three groups: active nocturnal enuresis (ANE, n = 225), history of nocturnal enuresis (HNE, n = 1171), and healthy control groups (CG, n = 2076). Multimodal neuroimaging protocol evaluated macrostructural properties via structural MRI (sMRI), microstructural white matter integrity via diffusion MRI (dMRI), and functional connectivity via resting-state fMRI (fMRI). Group differences were evaluated using linear models within an ANCOVA framework, adjusting for intracranial volume and handedness with False Discovery Rate (FDR) correction. RESULTS: Compared to controls, the ANE group exhibited a significant volume deficit in the right caudate, decreased sulcal depth in the left insula, and lower internal correlation within the Cingulo-Opercular Network (CON). Conversely, the dry HNE group demonstrated significant structural adaptations, including bilaterally larger putamen volumes and increased right caudate volume compared to the ANE group. The HNE group also showed increased microstructural density (decreased mean diffusivity) in the bilateral hippocampus and an increased cortical surface area in the left insula. Both NE groups demonstrated persistently reduced functional coupling within the CON. CONCLUSIONS: Nocturnal enuresis appears to be associated with a potential complex central signaling deficits. Reduced internal correlation within the CON across both active and former bedwetters indicates a potential for impairment in processing internal homeostatic bladder signals during sleep.

Humans↗

PubMed2026

Extending the Treatment Window for Intravenous Thrombolysis in Acute Ischemic Stroke: An Updated Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Intravenous thrombolysis (IVT) is the standard treatment for acute ischemic stroke within 4.5 hours of onset. However, imaging-based selection may extend the treatment window. This systematic review and meta-analysis evaluated the efficacy and safety of IVT administered beyond 4.5 hours after stroke onset or last known well (LKW) in patients selected based on imaging findings. METHODS: A comprehensive search of PubMed, Scopus, and Cochrane Library was performed to identify randomized controlled trials comparing IVT with alteplase or tenecteplase (TNK) administered >4.5 hours after stroke onset/LKW vs standard care. Primary outcomes were 3-month excellent (modified Rankin Scale [mRS] 0-1) functional outcome and symptomatic intracranial hemorrhage (sICH). Secondary outcomes included good (mRS 0-2) functional outcome, recanalization, and 3-month mortality. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup analysis assessed differences between alteplase and TNK. RESULTS: Fourteen studies involving 4,944 patients were included. The mean age was 69.8 years, 58.2% were male, the median National Institutes of Health Stroke Scale score was 9, and 12.3% received preplanned endovascular thrombectomy (EVT). A total of 2,492 patients received IVT in an extended time window (4.5-24 hours). Compared with standard care, extended IVT was associated with higher odds of achieving an excellent functional outcome (OR: 1.43 [95% CI 1.25-1.63]), a good functional outcome (OR: 1.25 [95% CI 1.11-1.40]), and recanalization (OR: 3.28 [95% CI 2.09-5.16]). There was no difference in 3-month mortality (OR: 1.21 [95% CI 0.95-1.53]). However, IVT increased the risk of sICH (OR: 2.51 [95% CI 1.47-4.28]). Sensitivity analysis excluding patients who received EVT showed no impact on the outcomes. TNK exhibited similar efficacy to alteplase but showed potentially lower odds of sICH (OR: 1.96, 95% CI 1.06-3.64) compared with alteplase (OR: 5.29, 95% CI 1.80-15.57); however, the subgroup difference was not significant (p = 0.11). DISCUSSION: Among patients selected based on imaging, 4.5-24 hours after stroke onset/LKW, IVT improves outcomes despite an increased risk of sICH. TNK showed similar efficacy to alteplase, with a possible lower risk of sICH; however, direct comparisons in future trials are needed.

Humans↗

PubMed2026

Assessment of the role and effectiveness of nurse-led multimodal intervention in the rehabilitation of dysphagia in patients with brain tumors.

BACKGROUND: Dysphagia is a common complication in patients with brain tumors, which has a profound adverse impact on patients' health status and quality of life. However, there is a relative lack of research on the rehabilitation of dysphagia in brain tumor patients, especially regarding the role and effectiveness of nurse-led multimodal interventions in the rehabilitation of dysphagia in brain tumor patients, which lacks systematic assessment and in-depth discussion. AIM: This study aimed to evaluate the role and effectiveness of a nurse-led multimodal intervention in improving swallowing function and quality of life in brain tumor patients with dysphagia. METHODS: In this study, a randomized controlled trial (RCT) design was used to select 120 dysphagia patients among brain tumor patients admitted to our hospital during the period of January 2024 to May 2024 as the study subjects, and they were stratified and randomly divided into an intervention group (n = 60) and a control group (n = 60). While the control group received conventional nursing care and treatment protocols, the intervention group received a nurse-led multimodal intervention program, including personalized swallowing training, nutritional support, psychological care, and a family-participatory rehabilitation program, which was developed and dynamically adjusted by nurses, rehabilitation therapists, and dietitians. Differences in data before and after the intervention were analyzed using the paired t-test or Wilcoxon signed-rank test, and between-group comparisons were made using the independent samples t-test or Mann-Whitney U test. RESULTS: Both the intervention and control groups showed improvement in swallowing function among the patients. The Kubota drinking test score, Saito's swallowing function grading, and the quality of life scores for patients in the intervention group showed a significant enhancement compared to those in the control group (P < 0.05), indicating that the intervention was more effective than the control. When compared within groups, all scores in both the intervention and control groups improved gradually with the time of intervention (P < 0.05). The improvement was significantly higher in the intervention group than in the control group. CONCLUSION: This study demonstrates that a nurse-led multimodal intervention is significantly effective in improving swallowing function and quality of life in patients with brain tumors. The intervention provides comprehensive rehabilitation support for patients through multidisciplinary collaboration and personalized care and has certain clinical promotion value.

Humans↗

PubMed2026

Depth-dependent microbial succession and interspecies hydrogen transfer drive pit mud maturation in Chinese strong-flavor baijiu fermentation.

Microbial communities in fermentation pit mud play a key role in determining the quality of Chinese strong-flavor baijiu (CSFB). However, the ecological processes underlying pit mud maturation across spatial and temporal scales remain unclear. In this study, amplicon sequencing and metagenomic analyses were employed to investigate the taxonomic succession, community assembly, and metabolic functions of bacterial and archaeal communities during the transition from fresh pit mud (FPM) to new pit mud (NPM) and old pit mud (OPM). A pronounced depth-dependent succession pattern was observed, with 4 cm representing a critical ecological boundary separating distinct community structures and maturation trajectories. During surface-layer maturation, community assembly shifted from stochastic to deterministic processes, accompanied by homogeneous selection and increasing network complexity. In contrast, stochastic processes remained dominant throughout deep-layer maturation. Metagenomic analyses revealed a functional transition from lactate and acetate production, primarily associated with Lactobacillus in FPM and NPM, to butyrate and caproate production associated with Clostridium and Caproiciproducens in OPM. This functional transition was accompanied by enhanced amino acid metabolism, which was associated with the enrichment of Proteiniphilum and Aminobacterium. Notably, methanogen-mediated interspecies hydrogen transfer (IHT) emerged as a key ecological feature during pit mud maturation. In OPM, IHT networks primarily involving Methanobacterium and Methanosarcina linked methanogenesis with reverse β-oxidation through diverse hydrogen-transfer pathways, reinforcing metabolic interactions underlying caproate production. These findings provide new insights into the ecological mechanisms underlying pit mud maturation and offer a theoretical basis for the directed cultivation of high-quality pit mud in CSFB production.

Hydrogen↗

PubMed2026

Pathogenic Variants in HEPACAM Alter Protein Localization and Interactome in Astrocytes of the Developing Mouse Cortex.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare leukodystrophy characterized by early-onset macrocephaly, white matter edema, seizures, and motor and cognitive decline. Approximately 25% of MLC patients carry HEPACAM pathogenic variants, many of which are dominant missense variants causing remitting MLC Type 2b. HEPACAM encodes hepatic and glial cell adhesion molecule (hepaCAM), also known as GlialCAM, an astrocyte-enriched transmembrane protein with important roles in astrocyte territory establishment, gap junction coupling, branching organization, synaptic function, and development of the gliovascular unit. The molecular mechanisms through which pathogenic variants in HEPACAM alter hepaCAM protein function in vivo and facilitate MLC pathogenesis during brain development remain largely unknown. Here, we used new viral tools and proximity-based proteomics to examine how three different dominant pathogenic variants alter hepaCAM subcellular localization and protein interactome in astrocytes of the developing mouse cortex. We found dramatic changes in hepaCAM distribution throughout the astrocyte, which were common to all mutants tested. We also observed significant changes in protein interactome between wild type and mutant hepaCAM, including decreased association with previously described hepaCAM-interacting proteins Connexin 43 and CLC-2. Moreover, we identified the epilepsy-associate potassium channel KCNQ2 as a novel hepaCAM interaction partner and found reduced association between KCNQ2 and pathogenic variants. Collectively, our data provide new insights into hepaCAM protein function in astrocytes during brain development, reveal altered protein dynamics of pathogenic variants, and provide a new resource to explore the molecular underpinnings of MLC pathogenesis.

Animals↗

PubMed2026

Occlusion site and outcomes in intra-arterial tenecteplase after successful endovascular therapy: a secondary analysis of the ANGEL-TNK trial.

BACKGROUND: Endovascular thrombectomy achieves macroreperfusion in large vessel occlusion (LVO) stroke, but only one-quarter of patients had excellent functional outcome. Adjunct intra-arterial (IA) tenecteplase could further improve the treatment effect, yet its efficacy across internal carotid artery (ICA) versus middle cerebral artery (MCA) M1/M2 occlusion remains unclear. OBJECTIVE: To evaluate whether IA tenecteplase improves 90-day functional outcomes in LVO patients stratified by occlusion site (ICA, MCA M1, MCA M2). METHODS: Prespecified secondary analysis of the ANGEL-TNK trial (multicenter, randomized, open-label, blinded endpoint) in 19 Chinese stroke centers. Participants were enrolled who had anterior circulation LVO, 4.5-24 hours from symptom onset, and CT angiography (CTA)/magnetic resonance angiography (MRA)-proven ICA, M1, or M2 occlusion. INTERVENTION: Randomization (1:1) to IA tenecteplase (0.125 mg/kg) or standard medical management after expanded Thrombolysis in Cerebral Infarction (eTICI) 2b50-3 reperfusion. MAIN OUTCOME MEASURE: The primary outcome was the rate of 90-day modified Rankin Scale (mRS) 0-1. RESULTS: There were 256 patients in the trial, including 71 (27.7%) ICA, 122 (47.6%) MCA M1, and 62 (24.2%) MCA M2. ICA occlusion patients treated with IA tenecteplase had higher rates of 90-day mRS 0-1 (39.4% vs 13.2%; relative risk (RR) 2.99; 95% CI 1.51 to 5.96; p=0.002) and mRS 0-3 (54.5% vs 42.1%; RR 1.30; p=0.048) versus controls, with a significant shift toward better mRS scores (median 3 (IQR 1-4) vs 4 (2-6); odds ratio (OR) 2.26; p<0.001). Post hoc analysis showed higher eTICI progression in ICA patients (51.5%) versus MCA M1 (37.9%) and M2 (25.7%). IA tenecteplase had a lower any intracranial hemorrhage within 48 hours in ICA patients (15.2% vs 39.5%; RR 0.38; p<0.001) compared with standard medical management. No significant benefits were observed in the MCA M1/M2 subgroups, and interaction effects were significant between ICA and MCA segments for functional outcomes and safety. CONCLUSIONS AND RELEVANCE: IA tenecteplase had a better functional outcome and lower hemorrhage risk in ICA occlusion compared with standard medical management but not in MCA M1/M2. Occlusion site is a critical determinant of response to IA tenecteplase. A pooled analysis of IA tenecteplase stratified by occlusion site strata is warranted.

Humans↗

PubMed2026

Efficacy and Safety of Celecoxib Combined With Jintiange Capsules for the Treatment of Knee Osteoarthritis: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND Knee osteoarthritis (KOA) poses a substantial global health burden, and conventional nonsteroidal anti-inflammatory drug (NSAID) therapy with celecoxib is hindered by adverse effects. This study evaluated the efficacy and safety of combining celecoxib with Jintiange capsules, a synthetic tiger bone formulation used in traditional Chinese medicine (TCM), to manage symptomatic KOA. MATERIAL AND METHODS This 12-week, randomized, double-blind, placebo-controlled trial enrolled 120 patients with KOA (age 40 years; visual analog scale [VAS] score 4-7). Participants received celecoxib (200 mg/day tapered to 100 mg/day) combined with either Jintiange capsules (3.6 g/day) or placebo. The primary outcome was the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score. Secondary outcomes included WOMAC subscale scores (pain, function, and stiffness), VAS scores, and adverse drug reaction reports. RESULTS The experimental group demonstrated a 23.5-point (37.8%) reduction in WOMAC total score from baseline (P<0.001); the control group showed a 13.2-point (21.6%) reduction (P<0.001). The experimental group achieved 51.6% improvement in the WOMAC pain subscale (P<0.001), whereas the control group showed 33.3% improvement (P<0.001). Relative to the control group, the experimental group demonstrated a greater reduction in VAS score (P<0.001). Combined TCM-NSAID therapy produced significantly greater pain relief and functional improvement than NSAID monotherapy. CONCLUSIONS Celecoxib combined with Jintiange capsules provided clinically meaningful improvements in pain relief and functional outcomes relative to celecoxib monotherapy in patients with KOA. These findings support integration of TCM with conventional pharmacotherapy for osteoarthritis management.

Humans↗

PubMed2026

Retinoid dynamics in immune cells during age-related diseases.

Retinoids comprise vitamin A and its structurally related natural and synthetic derivatives. Retinoid dynamics involves multiple retinoid forms, carrier proteins, and enzymes that orchestrate the absorption, transport, storage and biotransformation of dietary vitamin A. Beyond their canonical metabolic functions, metabolites and proteins involved in retinoid metabolism also play distinct roles in signal transduction and transcriptome reprogramming, broadening the mechanisms that influence immune cell fate decisions. Age‑related changes in retinoid bioavailability and signaling intensity alter immune cell polarization and function, thereby contributing to the pathogenesis of chronic inflammation in neurodegenerative diseases, cardiovascular diseases, osteoarthritis, and other age-related diseases. In this review, we focus on age-related alterations in the retinoid metabolic pathway and their impact on inflammation and the progression of age-related diseases. This review highlights the pivotal role of retinoid metabolism in anti-ageing interventions and considers future directions and challenges in this field.

Humans↗

PubMed2026

Tranexamic acid in spontaneous intracerebral hemorrhage: an updated systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Tranexamic acid (TXA) is a well-established antifibrinolytic medication in the general population. However, its efficacy and safety for patients with spontaneous intracerebral hemorrhage (ICH) remain inconclusive. Consequently, we conducted a systematic review and meta-analysis to assess the effectiveness and safety of TXA for spontaneous ICH. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) following established methodological standards. Our search encompassed eight electronic databases from inception to April 25, 2024. The primary outcome was a reduction in all-cause mortality. The secondary outcomes included improvements in functional independence, neurological impairment, activities of daily living, and reduction in hematoma expansion (HE). Fixed-effects or random-effects model were performed for pooled data where eligible. RESULTS: A total of 9 RCTs that initially enrolled 3,124 patients were included. There were no significant differences observed concerning all-cause mortality (RR, 1.03; 95% CI [0.89-1.18]), hematoma expansion (RR, 0.90; 95% CI [0.80-1.00]), improvement of functional independence (RR, 1.02; 95% CI [0.92-1.12], neurological impairment (MD, -0.88 [95% CI, -2.22-0.45]), or activities in daily living (MD, -0.83 [95% CI, -29.25-12.59]). The pooled data indicated that TXA for ICH was associated with a decrease in hematoma volume from baseline (MD, -1.74; 95% CI [-2.47 to -1.02]). No significant difference in adverse events was observed between the TXA group and the control group. CONCLUSIONS: In summary, TXA does not affect all-cause mortality, functional outcomes, or neurological impairment, nor does it reduce HE, despite reducing hematoma volulume. TXA use for ICH requires careful clinical consideration.

Humans↗